The overall goal of the research proposed herein is the incorporation of 77Se by chemical synthesis, chemical modification, enzymic catalysis, and in vivo systems into biomolecules and the subsequent investigation of the structure and function of the selenium-labeled biomolecules by 77Se NMR spectroscopy together with biochemical procedures. Initially we describe those features of 77Se NMR which make it suitable as a probe for the structure and behavior of biomolecules. We then provide four major research problems which represent the prime emphasis of these studies. These investigations involve the chemical replacement of sulfur by selenium in representative biomolecules, including cysteine, glutathione, oxytocin, papain, ribonuclease, and tRNA, followed by their subsequent characterization via 77Se NMR and biochemical techniques. Of the many other systems to which 77Se NMR could be applied fruitfully, we have highlighted studies of Se-Coenzyme A, Se-adenosyl selenomethione, Se-folates, and selenopyridine nucleotides. Finally we conclude by commenting on the possibilities for investigating naturally occurring selenobiomolecules via 77Se NMR.